Saliva lubricates the mouth and also contains bacteriostatic and digestive agents. Strong tasting and dry foods are typically the most effective in stimulating saliva production. Saliva stimulation can also follow the consumption of distasteful materials, as a defensive response of the oral mucosa.
Xerostomia (dry mouth) is suffered by an estimated 20% or more of adults, most of whom are women, as a consequence of the inability to secrete saliva. The condition itself is uncomfortable, but may also have serious consequences, resulting in severe dental decay and/or oral infections. Dry mouth can be caused by a number of maladies, such as an autoimmune disease like Sjögren's syndrome, diabetes, AIDS, bone marrow transplantation or dehydration. It may also occur as a response to radiation treatment or as an unwanted side effect of drug treatments. It is thought that over 1,800 drugs have the capacity to cause dry mouth, when taken over a period of time. Dry mouth may also occur as a physiologic response (e.g. stress, nervousness, or “stage fright”).
Individuals suffering from Sjögren's syndrome or other pathologic causes of xerostomia chronically lack the ability to salivate and have difficulty tasting, chewing, swallowing, and speaking. Severe cases of xerostomia can bring about heightened tooth decay and infections of the mouth.
Xerostomic individuals may benefit from drug treatment with pilocarpine, for example, which stimulates salivation. However, other secretory functions are heightened as well, which can include profuse sweating. In these cases, the curative treatment may be as objectionable as xerostomia.
Palliative treatments are generally short acting and cosmetic in nature, and include constant ingestion of water, the use of non-cariogenic candies or demulcents, or other agents to directly hydrate the oral cavity or to provide a lubricious mouthfeel. Traditional lozenges, such as candy or cough drops, begin to dissolve immediately upon placement in the oral cavity, and rapidly dissolve within a few minutes. Although individuals' responses to such treatments can vary, these treatments do not provide relief for the long-term and chronic nature of xerostomia.
There is anecdotal evidence that some traditional herbal or natural products may stimulate salivation. For the most part, these reports concern the chewing of plant materials such as stems, bark, seeds, and leaves, etc. Some plant materials used have broadly stimulating properties, such as betel, khat, tobacco and cola nuts. Most plant materials have strong tastes, such as sour tasting lemon and citrus peel, and bitter tasting wormwood, golden seal and yarrow stems, or contain unpleasant-tasting irritants, such as the resins of gum myrrh and the pepper of kava and prickly ash bark.
Compositions for the treatment of plaque, which are also capable of stimulating the production of saliva, require abrasive materials. For example, U.S. Pat. No. 5,804,165 to Arnold discloses an anti-plaque oral composition containing a source of carbon dioxide, silica, and xylitol where the carbon dioxide comes from a bicarbonate. The tablet converts to a solid silica-containing suspension in the saliva of an oral cavity (see also U.S. Pat. Nos. 5,817,294; 5,965,110; and 6,086,854, all to Arnold). The presence of abrasive materials, such as silica, however, may harm the dry mucosal tissue, if administered to a patient suffering from xerostomia. Additionally, these compositions only provide a short-term effect.
Bioadhesive sticker tablets for the treatment of oral disorders, such as ulcers or legions are disclosed in U.S. Publication No. 2007/0104783 to Domb, et al. However, the tablets are not indicated for the treatment of xerostomia.
Treatments of xerostomia have been directed toward the control of dental decay, relief of symptoms, and increased salivary flow. The currently available treatments range from over the counter (OTC) medications to prescription drugs. Effective drugs appear to be few; and a large number of prescription drugs cause or exacerbate xerostomia.
Artificial saliva and saliva substitutes are available in the form of solutions, sprays and lozenges to replace moisture and lubricate the mouth; however, they must be used frequently and consistently as they do not stimulate salivary function.
U.S. Pat. No. 5,580,880 to Handa, et al., U.S. Pat. No. 5,686,094 to Acharya, U.S. Pat. No. 5,962,503 to Ekstrom, et al., and U.S. Pat. No. 7,198,779 to Rifa Pinol, et al., disclose compositions containing spirooxathiolane-quinone, polycarbophil, cholinesterase inhibitors, and a combination of saline saliva stimulating substitute agents, saliva production stimulating agent, oral antiseptic and oral mucosal protective agents respectively, for the treatment of xersotomia. However, these compositions do not remain long in the mouth and do not produce a long-lasting effect.
There has been some success clinical reported in treating xerostomia. However, given the large number of patients suffering from xerostomia each year, in addition to the larger number of patients undergoing cancer therapy, who often receive multiple cycles of radiation therapy and/or chemotherapy, there is a need for improved treatments for xerostomia. Further, many current treatments provide unpleasant side effects, such as profuse sweating, or require multiple administrations throughout the day to be effective.
It is therefore an object of the invention to provide improved compositions for the treatment of xerostomia and methods of use thereof.